The Scientific Core is designed to successfully recruit and monitor HCV-antibody-negative young injection drug users for HCV infection and to clinically characterize acute infection. Better understanding of spontaneous recovery of HCV infection is necessary to improve methods to prevent and treat chronic infection. A major limitation is the rare recognition of acute infection in humans. We have overcome this obstacle by following persons at risk for HCV infection monthly. By screening for HCV infection and careful monitoring of acutely infected persons, we have established an acute infection repository that has already been used by immunologists to advance our understanding of acute hepatitis C recovery and persistence. For this application, the Core aims to recruit and monitor HCV antibody negative young injection drug users, to clinically characterize acute infection when it occurs, and to establish and maintain an acute infection repository and distribute the resources to NIH funded investigators. By accomplishing these aims, the Clinical Core will make a major contribution to our understanding of hepatitis C recovery and achieve many of the objectives of RFA-AI-09-025. This cohort will allow us to prospectively follow subjects at risk for infection with blood testing including liver enzymes, HCV genotype, and HCV RNA levels and perform serial serum and lymphocyte collection and banking, allowing determination of the timing and outcome of infection and factors associated with outcome. This acute infection repository will distribute its resources for use in projects 1 and 2 as well as to other NIH funded investigators.